aprikalim and Coronary-Artery-Disease

Constriction in response to serotonin is enhanced in the coronary arteries of atherosclerotic monkeys. The main objective of the present study was to determine whether abnormal responses to serotonin in atherosclerosis are reversed following removal of dietary cholesterol. In addition, we examined the effect of an atherogenic diet and reduction in dietary cholesterol on vascular responses to activation of ATP-sensitive K+ channels with aprikalim. Diameters of small coronary arteries were measured on the epicardial surface of the left ventricle in vivo by using stroboscopic illumination synchronized to the heart cycle to visually freeze the motion of the heart. Diameters were measured with a microscope-video system during topical application of two vasoconstrictor agonists, serotonin and the thromboxane mimetic U46619, and the vasodilator agonists aprikalim and nitroprusside. Responses were compared in normal (n = 9), atherosclerotic (n = 14; high-cholesterol diet), and regression (n = 8; high-cholesterol diet followed by normal diet) monkeys. Constriction of coronary arteries in response to serotonin was enhanced in monkeys on an atherogenic diet and was normal in regression monkeys. Vasoconstriction in response to U46619 and vasodilation in response to nitroprusside and aprikalim were not altered by atherosclerosis. Thus, abnormal vascular responses to serotonin in small coronary arteries of atherosclerotic monkeys without morphological evidence of disease can be reversed to normal by reducing dietary cholesterol.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adenosine Triphosphate; Animals; Cholesterol, Dietary; Coronary Artery Disease; Coronary Vessels; Macaca fascicularis; Male; Nitroprusside; Picolines; Potassium Channels; Prostaglandin Endoperoxides, Synthetic; Pyrans; Serotonin; Thromboxane A2; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents